Over the past few years, the exploration and utilization of combinatorial chemistry (and multi parallel synthesis) as a pharmaceutical drug discovery technology has rapidly evolved. The field of combinatorial/multi parallel chemistry has expanded to include not only solid and solution-phase methods for expedited compound synthesis, but also hybrid approaches which combine the purification advantages of solid-phase synthesis with the flexibility of solution-phase synthesis. (Kaldor, S. W. and Siegel, M. G., Curr. Opin. Chem. Biol. 1997, 1, 101-106 and Thompson, L. A. and Ellman J. A., Chem. Rev. 1996, 96, 555-600) Inherent in any approach to produce chemical libraries is the need to rapidly purify, isolate, and manipulate chemical library members during their preparation.
Polymeric scavenging reagents have emerged as useful tools for combinatorial synthesis, particularly, for solution-phase chemical library synthesis. These materials are employed to remove, or scavenge, unwanted reagents or bi-products and thus aid in the purification of materials. (Creswell, M. W. et. al., Tetrahedron, 1998, 54, 3983-3998; Kaldor, S. W. et. al., Tetrahedron Lett. 1996, 37, 7193-7196; Flynn, D. L. et. al., S., J. Am. Chem. Soc. 1997, 119, 4874-4882; Kaldor, S. W. et. al., Bioorg. Med. Chem. Lett. 1996, 24(6), 3041-3044; Caldarelli, M. et. al., J. Chem. Soc., Perkin Trans. 1. 1999, 107-110; Booth, R. J. and Hodges, J. C., J. Am. Chem. Soc. 1997, 119, 4882-4886; Gayo, L. M. and Suto, M. J., Tetrahedron Lett. 1997, 38, 513-516; and Siegel, M. G. et. al., Tetrahedron Lett. 1997, 38, 3357-3360). Typically, the polymeric scavengers are added after the chemical reaction is complete to remove excess reactants and bi-products. The resulting resin bound reactants are removed by simple filtration leaving the product in solution. Examples of polymeric scavenger reagents include:

All the above resins are made by initial synthesis of a polystyrene or polystyrene copolymer bead followed by one or more chemical modification steps to introduce the scavenging functionality. For example, the isocyanate functional bead which is sold as a scavenger for amines can be prepared from the Merrified resin via the amino methyl polystyrene:

The resins used are typically lightly crosslinked polystyrenes (1 to 3% divinyl benzene) which typically require solvents that will swell the resin to allow reagents to access the polymer bound functional groups. Alternatively the resin could be a macroporous resin (high divinylbenzene content) which has permanent porosity allowing reactants to access the functional groups independent of the solvent type.
Many of the scavenger supports that are employed in combinatorial applications are designed for the removal of organic reagents. One area of synthesis where the use of scavenger supports is potentially useful is for example in metal mediated reactions. Metal mediated reactions are useful in synthesis for performing a variety of chemical transformations, however typically the catalysts employed in these reactions are transition metal derived.
Additionally the removal of catalyst residues from metal-catalysed processes at the industrial scale is becoming more important. Stricter regulations on the contamination of products and wastestreams have generated a higher need for alternative methods of removing heavy metals from these products and wastestreams. In particular in the pharmaceutical industry regulation by the Federal Drug Administration (FDA) has resulted in very low target levels of transition metals in Active Pharmceutical Ingredients (APIs). Additionally metal contamination in a pharmaceutical intermediate can interfere with chemistry carried out at a later stage in the manufacturing process.
There is therefore a need for functionalised supports which act as scavengers for metals, especially transition metals, and which show good chemical stability.